Background: Polymorphic light eruption is the most common photodermatosis characterized by nonscarring, pruritic, erythematous papules and plaques. Aim: To evaluate the efficacy and safety of hydroxychloroquine in comparison with chloroquine in patients suffering from polymorphic light eruption. Methods: This was a randomized, double-blind, comparative, multicentric study conducted at two centers. This study enrolled 68 (58.1%) males, 49 (41.8%) females whose ages ranged from 18-73 years and average weight was 57.89 ± 8.27 kg. A total of 117 patients were enrolled in the study. Out of 117 patients, 63 patients were randomized to receive hydroxychloroquine tablets 200 mg twice daily for the first month and 200 mg once daily for the next month. Similarly, 54 patients were randomized to receive chloroquine tablets 250 mg twice daily for the first month and 250 mg once daily for the next month. The total duration of therapy for both the study arms was two months. The severity and frequency of burning, itching, erythema and scaling were evaluated at predetermined intervals (at baseline, after four, eight and 12 weeks of therapy). Results: A significant reduction in severity scores for burning, itching, and erythema was observed in patients treated with hydroxychloroquine than with chloroquine ( P < 0.05). However, hydroxychloroquine was as good as chloroquine in reducing severity of scaling at the end of the study evaluation ( P = 0.229). The good to excellent response was reported by 68.9% of the patients who received hydroxychloroquine and by 63% of the patients who received chloroquine. The adverse events reported were mild to moderate and none of the patients reported any serious adverse events or ocular toxicity in this study. Conclusion: Hydroxychloroquine was found to be significantly more effective than chloroquine in the treatment of polymorphic light eruption and can be used safely in the dosage studied in such patients with little risk of ocular toxicity.